Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review summarizes current strategies in the treatment of patients with pleural effusion. To determine whether a patient has a transudative or exudative pleural effusion, Light's criteria should be applied to measure the concentrations of protein and lactate dehydrogenase (LDH) in the pleural fluid and serum. If the effusion is transudative, therapy should be directed toward the underlying congestive heart failure, cirrhosis, or nephrosis. Consideration should be given to pleurodesis with a sclerosant if patients with recurrent transudative effusion have severe dyspnea due to their effusion. If the effusion is exudative, attempts should be made to define the etiology. The diagnosis of pleural malignancy is most easily established via pleural fluid cytology. If this is negative and the patient is suspected of having pleural malignancy, thoracoscopy is indicated. The concentrations of adenosine deaminase and gamma-interferon in pleural fluid are useful in the diagnosis of pleural tuberculosis. Patients with pneumonia and pleural effusion should undergo therapeutic thoracentesis; the pleural fluid should be Gram-stained and cultured, and the differential cell count, glucose and LDH concentration, and pH should be determined. Indicators of a poor prognosis include the presence of frank pus, a positive Gram-stain, a pleural glucose concentration of less than 2.2 mmol/L, a pH less than 7.00, the presence of pleural loculations, and an LDH concentration greater than three times the upper limit of normal in serum. If the pleural fluid cannot be completely evacuated because of loculations, intrapleural thrombolytic therapy should be considered. If thrombolytics are ineffective, thoracoscopy or thoracotomy with decortication should be performed. Dyspneic patients with malignant pleural effusions whose dyspnea is relieved with therapeutic thoracentesis should be considered for pleurodesis using a tetracycline derivative. Talc is not recommended because it induces acute respiratory distress syndrome in about 5% of patients, with an overall mortality of 1%.
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PMID:Management of pleural effusions. 1092 61

Adenosine is a signaling nucleoside that is elevated in the lungs of asthmatics. We have engineered a mouse model that has elevated levels of adenosine as a result of the partial expression of the enzyme that metabolizes adenosine, adenosine deaminase (ADA). Mice with lowered levels of ADA enzymatic activity were generated by the ectopic expression of an ADA minigene in the gastrointestinal tract of otherwise ADA-deficient mice. These mice developed progressive lung inflammation and damage and died at 4-5 mo of age from respiratory distress. Associated with this phenotype was a progressive increase in lung adenosine levels. Examination of airway physiology at 6 wk of age revealed alterations in airway hyperresponsiveness. This was reversed following the lowering of adenosine levels using ADA enzyme therapy and also through the use of the adenosine receptor antagonist theophylline, implicating both the nucleoside and its receptors in airway physiological alterations. All four adenosine receptors were expressed in the lungs of both control and partially ADA-deficient mice. However, transcript levels for the A(1), A(2B), and A(3) adenosine receptors were significantly elevated in partially ADA-deficient lungs. There was a significant increase in alveolar macrophages, and monocyte chemoattractant protein-3 was found to be elevated in the bronchial epithelium of these mice, which may have important implications in the regulation of pulmonary inflammation and airway hyperresponsiveness. Collectively, these findings suggest that elevations in adenosine can directly impact lung inflammation and physiology.
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PMID:Adenosine-dependent airway inflammation and hyperresponsiveness in partially adenosine deaminase-deficient mice. 1159 98

Adenosine, a signaling nucleoside, exhibits tissue-protective and tissue-destructive effects. Adenosine levels in tissues are controlled in part by the enzyme adenosine deaminase (ADA). ADA-deficient mice accumulate adenosine levels in multiple tissues, including the lung, where adenosine contributes to the development of pulmonary inflammation and chronic airway remodeling. The present study describes the development of pulmonary fibrosis in mice that have been genetically engineered to possess partial ADA enzyme activity and, thus, accumulate adenosine over a prolonged period of time. These partially ADA-deficient mice live for up to 5 mo and die from apparent respiratory distress. Detailed investigations of the lung histopathology of partially ADA-deficient mice revealed progressive pulmonary fibrosis marked by an increase in the number of pulmonary myofibroblasts and an increase in collagen deposition. In addition, in regions of the distal airways that did not exhibit fibrosis, an increase in the number of large foamy macrophages and a substantial enlargement of the alveolar air spaces suggest emphysemic changes. Furthermore, important proinflammatory and profibrotic signaling pathways, including IL-13 and transforming growth factor-beta1, were activated. Increases in tissue fibrosis were also seen in the liver and kidneys of these mice. These changes occurred in association with pronounced elevations of lung adenosine concentrations and alterations in lung adenosine receptor levels, supporting the hypothesis that elevation of endogenous adenosine is a proinflammatory and profibrotic signal in this model.
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PMID:Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. 1625